Perinatal PCP treatment alters the developmental expression of prefrontal and hippocampal muscarinic receptors.
Perinatal phencyclidine (PCP) treatment has been used to model brain pathological processes that may be present in schizophrenia such as increased apoptosis during early brain development, and long-term alterations in expression of parvalbumin-containing interneurons and glutamatergic N-methyl-D-aspartate (NMDA) receptors. We report that this treatment also affects receptor expression of another excitatory neurotransmitter receptor, the muscarinic receptor. Female rat pups received injections of the NMDA receptor antagonist PCP (10 mg/kg, s.c.) or saline on postnatal days (PN)7, 9 and 11. [3H]Pirenzepine binding to M1/4 receptors was examined at four time-points (PN12, 18, 32 and 96) following treatment cessation. Significant effects of treatment on [3H]pirenzepine binding were evident immediately after treatment cessation with a decrease in PCP-treated rats at PN12 in the prefrontal cortex (-24%, p<0.05) and hippocampus (-19%, p<0.05). After this initial decrease, binding subsequently increased to 47% above control levels in the prefrontal cortex of adolescent animals, which remained elevated in adulthood (+10%, p<0.05), while in the hippocampus there was a trend towards increased binding in adolescent animals and no change thereafter. This work adds to findings demonstrating that perinatal PCP exposure leads to long-term imbalance of excitatory and inhibitory neurotransmitter systems, supporting its relevance as a developmental model of schizophrenia pathology. Alterations in muscarinic receptor expression may contribute specifically to the cognitive impairments reported to occur after perinatal NMDA receptor antagonist treatment.
du Bois
Teresa Marie
TM
Schizophrenia Research Institute (SRI), Sydney, Australia. tmdb66@uow.edu.au
Newell
Kelly Anne
KA
Han
Mei
M
Deng
Chao
C
Huang
Xu-Feng
XF
D000375:Aging / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D018727:Muscarinic Antagonists / Q000378:metabolism; D010622:Phencyclidine / Q000008:administration & dosage / Q000494:pharmacology*; D010890:Pirenzepine / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043643:Receptor, Muscarinic M1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043588:Receptor, Muscarinic M4 / Q000037:antagonists & inhibitors / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D043588:Receptor, Muscarinic M4; D010890:Pirenzepine; D010622:Phencyclidine